We will utilize AKR/J-streaker mice homozygous for the autosomal recessive mutation nustr (nude streaker) to assess the role of thymic epithelium (T.E.) in leukemogenesis in the AKR/J leukemic strain. Unlike AKR/J mice, the nustr/nustr mice are congenitally athymic, lack hair, do not develop recombinant retroviruses and have a low incidence of spontaneous leukemia. Like AKR/J mice, they are infected from birth with ecotropic murine leukemia viruses (MuLV). Low titers of splenic xenotropic MuLV have also been identified in nustr/nustr mice. The hypothesis states that AKR/J T.E. is required for transformation of nustr/nustr bone marrow cells into preleukemic cells and conversion of these preleukemic cells into leukemic cells during thymic differentiation. The aims are to determine if T.E. grafts are necessary for: (1) generation of recombinant MuLV in nustr/nustr mice; (2) leukemic transformation of nustr/nustr lymphoid cells; and (3) leukemia development after injection of cloned recombinant AKR MuLV into nustr/nustr mice. A fourth aim is to determine if preleukemic cells are present in the bone marrow of nustr/nustr mice. Aims 1 and 2 will be met by grafting irradiated autologous and allogeneic thymuses into nustr/nustr mice followed by observation for development of recombinant MuLV andleukemia. Aim 3 will involve injection of cloned, recombinant AKR/J MuLV into nustr/nustr mice grafted with neonatal thymuses, followed by observation for leukemia development. Aim 4 will involve transplantation of nustr/nustr bone marrow into sublethally irradiated (AKR X DBA/2)F1 recipients with observation of leukemia incidence. Phenotype analysis of all leukemiasthat develop in these experiments will be performed by flow cytometry to assess donor versus recipient origin of the leukemic cells and whether they are T, B, or null cell in origin. These studies will improve our knowledge of the role of the thymus in murine T-cell leukemogenesis. Childhood T-cell leukemia has a poor prognosis that could perhaps be improved by thymectomy (radiation or surgically induced) as a means of preventing relapses. There is preliminary evidence that irradiated neonatal thymus grafts from AKR mice amplify expression of MuLV in AKR-streaker mice approximately 6-8 months after transplantation. Grafts of irradiated autologous and allogeneic thymuses effectively reconstitute T-cell immunity in the AKR-streaker recipients. (IP)